Multi-chambered balloon catheter devices and methods

ABSTRACT

Catheter devices/systems and methods therefrom are described herein for treating acute kidney injury, especially the contrast-induced acute kidney injury wherein the devices may prevent the contrast dyes from entering into kidney and/or facilitate blood flow of kidney by said catheter system.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.16/447,830, filed Jun. 20, 2019, now U.S. Pat. No. 11,185,332, whichclaims the benefit of U.S Provisional Patent Application No. 62/688,233,filed Jun. 21, 2018, each of which are incorporated herein by reference.

The subject matter of the present application is related to the subjectmatter of U.S. patent application Ser. Nos. 15/140,502 (filed Apr. 28,2016), 15/189,460 (filed Jun. 22, 2016), 15/969,050 (filed May 2, 2018),and PCT Application Nos. PCT/US2014/072302 (filed Dec. 23, 2014) andPCT/US2017/031153 (filed May 4, 2017), and U.S. Provisional ApplicationNo. 62/688,323 (filed Jun. 21, 2018), the full contents of which areincorporated herein by reference.

BACKGROUND

Acute kidney injury (AKI), also called acute renal failure (ARF), is arapid loss of kidney function. The causes of AKI are numerous and mayinclude low blood volume, decreased blood flow to the kidneys, exposureof the kidney to toxic substances, or urinary tract obstruction. AKI isdiagnosed on the basis of clinical history and laboratory data. Kidneyfunction may be measured by serum creatinine or urine output, amongother tests, and a rapid reduction in either or both of these factorsmay be diagnosed as AKI.

One possible cause of AKI is the use of intravascular iodinated contrastmedia or contrast agents. Contrast-induced AKI (CI-AKI) is a commonproblem in patients receiving intravascular iodine-containing contrastmedia for angiography. CI-AKI is associated with excessivehospitalization cost, morbidity, and mortality. Clinical proceduresinvolving intravascular iodine-containing contrast media injection mayinclude, for example, percutaneous coronary intervention (PCI),peripheral vascular angiography and intervention, transarterial heartvalve interventions, and neurological angiography and intervention. Inclinical practice, CI-AKI is diagnosed when serum creatinine levelsincrease by more than either 25% or 0.5 mg/dL above baseline within 48to 72 hours of exposure to contrast media in the absence of otherculprit etiology for AKI.

Management of AKI hinges on identification and treatment of theunderlying cause. Additionally, management of AKI routinely includesavoidance of substances toxic to the kidneys, called nephrotoxins.Nephrotoxins include, for example, non-steroidal anti-inflammatory drugs(NSAIDs), such as ibuprofen, iodinated contrast agents, such as thoseused for CT scans, many antibiotics, such as gentamicin, and a range ofother substances.

Renal function monitoring by serum creatinine and urine output isroutinely performed. For example, insertion of a urinary catheter helpsmonitor urine output and relieves possible bladder outlet obstruction,such as with an enlarged prostate. In prerenal AKI without fluidoverload, administration of intravenous fluids is typically the firststep to improve renal function. Volume status may be monitored with theuse of a central venous catheter to avoid over- or under-replacement offluid. Should low blood pressure prove a persistent problem in thefluid-replete patient, inotropes such as norepinephrine and dobutaminemay be given to improve cardiac output and enhance renal perfusion.Also, while a useful pressor, there is no evidence to suggest thatdopamine is of any specific benefit, and may in fact be harmful.

The myriad causes of intrinsic AKI can require specific therapies. Forexample, intrinsic AKI due to Wegener's granulomatosis may respond tosteroid medication while toxin-induced prerenal AKI often responds todiscontinuation of the offending agent, which may, for example, beaminoglycoside, penicillin, NSAIDs, or paracetamol. Obstruction of theurinary tract may also cause AKI and treatment may require relief of theobstruction, for example with a nephrostomy or urinary catheter.

Renal replacement therapy, such as with hemodialysis, may be institutedin some cases of AKI. A systematic review of the literature in 2008shows no difference in outcomes between the use of intermittenthemodialysis and continuous venovenous hemofiltration (CVVH). Amongcritically ill patients, intensive renal replacement therapy with CVVHdoes not appear to improve outcomes compared to less intensiveintermittent hemodialysis.

Current prevention strategies for AKI, particularly for CI-AKI, aremainly supportive. They include, for example, (1) evaluating andstratifying patients with Mehran risk score before performing PCI, (2)avoiding high-osmolar contrast media by using low-osmolar or iso-osmolarcontrast media, (3) reducing the amount of contrast media during PCI,(4) applying intravenously isotonic sodium chloride solution or sodiumbicarbonate solution hours before and after PCI, and (5) avoiding use ofnephrotoxic drugs (such as nonsteroidal anti-inflammatory drugs,aminoglycosides antibiotics, etc.). (See Stevens 1999, Schweiger 2007,Solomon 2010.) However, none of these strategies have proven to beconsistently effective in preventing CI-AKI.

References relevant to the present disclosure may include: U.S. Pat. No.5,879,499, WO1996040347, WO2010018569, U.S. Pat. Nos. 6,913,600,6,251,093, US20050148997, U.S. Pat. No. 9,861,794, WO2015100393,CN201692487, U.S. Pat. Nos. 6,692,484, 6,036,697, US20130123621,US20050203553, US2005203558, and US20140051968.

SUMMARY

Aspects of the present disclosure provide devices for occludingvasculature of a subject. An exemplary device may comprise a cathetershaft and an inflatable balloon. The catheter shaft may comprise aproximal portion and a distal portion. The inflatable balloon may bedisposed on the proximal portion of the catheter shaft. The inflatableballoon may comprise a first balloon chamber and a second balloonchamber. The first and second balloon chambers may be formed by one ormore of (i) fixedly attaching a first length of the inflatable balloonto the catheter shaft along a longitudinal axis of the catheter to forma first longitudinal bond extending thereon or (ii) fixedly attaching asecond length of the inflatable balloon to the catheter shaft along thelongitudinal axis of the catheter to form a second longitudinal bondextending thereon. The inflatable balloon may have an expandedconfiguration which, when advanced into a blood vessel and positionedadjacent blood vessel ostia of the subject, may be sized to occlude theblood vessel ostia while allowing blood flow over the catheter shaft.The distal portion may be configured to remain outside a body of thesubject when the proximal portion is positioned adjacent blood vesselostia of the subject.

The first balloon chamber may be disposed on a first lateral side of theproximal portion and the second balloon chamber may be disposed on asecond lateral side of the proximal portion. The first balloon chamberand second balloon chamber may each be longitudinal cylindrical balloonchambers. The first balloon chamber and the second balloon chamber maybe in fluid communication with one another. The first balloon chamberand the second balloon chamber may be configured to inflatesimultaneously. The first longitudinal bond fixedly attaching theinflatable balloon to the catheter shaft may extend 80% of the length ofthe inflatable balloon. The second longitudinal bond may extend 90% ofthe length of the inflatable balloon. The inflatable balloon maycomprise a figure-eight, dumbbell, or butterfly-like cross section aboutthe catheter shaft disposed therein.

The device may further comprise one or more position indication featuresdisposed on the expandable balloon. The one or more position indicationfeature may comprise one or more radio-opaque markers, which maycomprise one or more radio-opaque longitudinal marker. The one or moreradio-opaque longitudinal markers may comprise a plurality ofradio-opaque longitudinal markers disposed on the expandable balloonalong a longitudinal axis of the expandable balloon. The one or moreradio-opaque longitudinal markers may be configured to indicate theorientation of the expandable balloon when positioned adjacent renalartery ostia of the subject. The one or more radio-opaque longitudinalmarkers may be configured to change from a straight configuration to abowed configuration when expanded adjacent blood vessel ostia of thesubject.

The first and/or second lengths of the inflatable balloon may be fixedlyattached to the catheter shaft by adhering or bonding the inflatableballoon to the catheter shaft, such as with an adhesive or thermal bond.

The device may be configured for preventing acute kidney injury fromcontract agent introduced into vasculature of the subject. The bloodvessel may be an abdominal aorta and the blood vessel ostia may be renalartery ostia.

Aspects of the present disclosure also provide systems for occludingvasculature of a subject. An exemplary system may comprise a cathetershaft, an inflatable balloon, and a time-delayed release mechanism. Thecatheter shaft may comprise proximal portion and a distal portion. Theinflatable balloon may be disposed on the proximal portion or thecatheter shaft. The time-delayed release mechanism may be incommunication with the inflatable balloon. The inflatable balloon maycomprise a first balloon chamber and a second balloon chamber. The firstand second balloon chambers may be formed by one or more of (i) fixedlyattaching a first length of the inflatable balloon to the catheter shaftalong a longitudinal axis of the catheter to form a first longitudinalbond extending thereon or (ii) fixedly attaching a second length of theinflatable balloon to the catheter shaft along the longitudinal axis ofthe catheter to form a second longitudinal bond extending thereon. Theinflatable balloon may have an expanded configuration which, whenadvanced into a blood vessel and positioned adjacent blood vessel ostiaof the subject, may be sized to occlude the blood vessel ostia whileallowing blood flow over the catheter shaft. The distal portion may beconfigured to remain outside a body of the subject when the proximalportion is positioned adjacent blood vessel ostia of the subject. Thetime-delayed release mechanism may be configured to collapse theinflatable balloon after a pre-determined amount of time followingexpansion of the inflatable balloon.

The first balloon chamber and second balloon chamber may each belongitudinal cylindrical balloon chambers. The first balloon chamber andthe second balloon chamber may be in fluid communication with oneanother. The first balloon chamber and the second balloon chamber may beconfigured to inflate simultaneously. The first longitudinal bond mayextend 80% of the length of the inflatable balloon. The secondlongitudinal bond may extend 90% of the length of the inflatableballoon. The inflatable balloon may comprise a figure-eight, dumbbell,or butterfly-like cross section about the catheter shaft disposedtherein.

The time-delayed release mechanism may comprise an energy accumulationand storage component. The energy accumulation and storage component maycomprise a spring. The energy accumulation and storage component maycomprise a syringe comprising a plunger, and wherein the spring iscoupled to the plunger.

The system may further comprise one or more position indication featuresdisposed on the expandable balloon. The one or more position indicationfeature may comprise one or more radio-opaque markers, which maycomprise one or more radio-opaque longitudinal marker. The one or moreradio-opaque longitudinal markers may comprise a plurality ofradio-opaque longitudinal markers disposed on the expandable balloonalong a longitudinal axis of the expandable balloon. The one or moreradio-opaque longitudinal markers may be configured to indicate theorientation of the expandable balloon when positioned adjacent renalartery ostia of the subject. The one or more radio-opaque longitudinalmarkers may be configured to change from a straight configuration to abowed configuration when expanded adjacent blood vessel ostia of thesubject.

The first and/or second lengths of the inflatable balloon may be fixedlyattached to the catheter shaft by adhering or bonding the inflatableballoon to the catheter shaft, such as with an adhesive or thermal bond.

The system may be configured for preventing acute kidney injury fromcontract agent introduced into vasculature of the subject. The bloodvessel may be an abdominal aorta and the blood vessel ostia may be renalartery ostia.

Aspects of the present disclosure also provide methods of preventingacute kidney injury from contract agent introduced into vasculature of asubject. In an exemplary method, a proximal portion of a catheter devicecomprising a catheter shaft and an inflatable balloon may be positionedin an abdominal aorta of the subject adjacent renal artery ostia of thesubject. The inflatable balloon may comprise a first balloon chamber anda second balloon chamber. The first and second balloon chambers may beformed by one or more of (i) fixedly attaching a first length of theinflatable balloon to the catheter shaft along a longitudinal axis ofthe catheter to form a first longitudinal bond extending thereon or (ii)fixedly attaching a second length of the inflatable balloon to thecatheter shaft along the longitudinal axis of the catheter to form asecond longitudinal bond extending thereon. The first and second balloonchambers of the inflatable balloon of the catheter device may beinflated to occlude the renal artery ostia. A bolus of the contrastagent may be introduced into the abdominal aorta of the subject whilethe inflatable balloon may be inflated to occlude the renal arteryostia, thereby preventing the contrast agent from entering into renalarteries of the subject. The first and second balloon chambers of theinflatable balloon may be deflated after the bolus of the contrast agenthas been introduced, thereby allowing blood flow to the renal arteriesto resume.

One or more position indication feature may be disposed on theinflatable balloon. The proximal portion of the catheter device may bepositioned by observing one or more of a position or orientation of theone or more position indication features and positioning the proximalportion of the catheter device in response to the observed position ororientation. The one or more position indication features may compriseone or more radio-opaque markers, which may be observed via x-rayimaging. The one or more radio-opaque longitudinal markers may beconfigured to change from a straight configuration to a bowedconfiguration when expanded adjacent blood vessel ostia of the subject.Occlusion of the renal artery ostia may be confirmed when the inflatableballoon is inflated. Wherein the one or more position indicationfeatures comprise one or more radio-opaque longitudinal markers, theocclusion of the renal artery ostia may be confirmed by observing theappearance of a bowed section in the one or more radio-opaquelongitudinal markers using x-ray imaging.

The first balloon chamber and second balloon chamber may each belongitudinal cylindrical balloon chambers. The first balloon chamber andthe second balloon chamber may be in fluid communication with oneanother. The first and second balloon chambers may be inflatedsimultaneously. The first and second balloon chambers may be deflatedafter a pre-determined amount of time. The inflation of the first andsecond balloon chambers and the introduction of the bolus of thecontrast agent may be synchronized.

The first and/or second lengths of the inflatable balloon may be fixedlyattached to the catheter shaft by adhering or bonding the inflatableballoon to the catheter shaft, such as with an adhesive or thermal bond.

Aspects of the present disclosure also provide methods of manufacturingdevices for occluding vasculature of a subject. In an exemplary method,a balloon catheter device comprising (i) a catheter shaft comprising aproximal portion and a distal portion and (ii) an inflatable ballooncomprising a distal end and a proximal end and disposed on the proximalportion of the catheter shaft may be provided. The inflatable balloonmay be fixedly attached to the catheter shaft at distal and proximalends of the inflatable balloon to form fluid-tight seals. A first lengthof the inflatable balloon may be fixedly attached to the catheter shaftalong a longitudinal axis of the catheter to form a first longitudinalbond extending thereon.

The inflatable balloon may comprise a cylindrical balloon.

Bonding of the first length of the inflatable balloon may deform theinflatable balloon such that the inflatable balloon has a heart-shapedcross-section about the catheter shaft.

The first longitudinal bond may extend at least 80% of the length of theinflatable balloon.

A second length of the inflatable balloon may be bonded to the cathetershaft along the longitudinal axis of the catheter shaft to form a secondlongitudinal body extending thereon. The bonding of the second length ofthe inflatable balloon may split the inflatable balloon into a firstballoon chamber and a second balloon chamber. The first balloon chambermay be disposed on a first lateral side of the proximal portion, and thesecond balloon chamber may be disposed on a second lateral side of theproximal portion. The inflatable balloon may comprise a cylindricalballoon, and the first balloon chamber and second balloon chamber mayeach comprise longitudinal cylindrical balloon chambers. The firstballoon chamber and the second balloon chamber may be in fluidcommunication with one another. The second longitudinal bond may extendat least 80% of the length of the inflatable balloon.

The inflatable balloon may have an expanded configuration which, whenadvanced into a blood vessel and positioned adjacent blood vessel ostiaof the subject, may be sized to occlude the blood vessel ostia whileallowing blood flow over the catheter shaft. The blood vessel may be anabdominal aorta, and the blood vessel ostia may be renal artery ostia.

The first length of the inflatable balloon may be fixedly attached tothe catheter shaft by one or more of adhering or bonding the firstlength of the inflatable balloon to the catheter shaft, such as with anadhesive or thermal bond. Likewise, the second length of the inflatableballoon may be fixedly attached to the catheter shaft by one or more ofadhering or bonding the second length of the inflatable balloon to thecatheter shaft, such as with an adhesive or thermal bond.

The balloon catheter device may be provided by providing the cathetershaft comprising the proximal portion and the distal portion, providingthe inflatable balloon comprising the proximal end and the distal end,disposing the inflatable balloon on the proximal portion of the cathetershaft, fixedly attaching the distal end of the inflatable balloon to thecatheter shaft to form a fluid-tight seal, and fixedly attaching theproximal end of the inflatable balloon to the catheter shaft to form afluid-tight seal.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the present disclosure are set forth withparticularity in the appended claims. A better understanding of thefeatures and advantages of the present disclosure will be obtained byreference to the following detailed description that sets forthillustrative embodiments, in which the principles of the presentdisclosure are utilized, and the accompanying drawings of which:

FIG. 1 illustrates a device comprising a balloon catheter having aninflatable balloon positioned in the supra-renal aorta near the orificesof the bilateral renal arteries for treating AKI, according to manyembodiments.

FIG. 2 shows the device illustrated in FIG. 1, wherein the inflatableballoon is inflated to occlude the orifices of both sides of the renalarteries, according to many embodiments.

FIGS. 3A-3F show various inflatable balloons suitable for use with thedevice of FIG. 1, according to many embodiments. FIG. 3A shows a sideview of a cylinder-like inflated balloon. FIG. 3B shows a cross-sectionview of the cylinder-like inflated balloon of FIG. 3A. FIG. 3C shows aside view of the morphology of an exemplary inflated balloon which is“butterfly-like”. FIG. 3D shows a cross-section view of thebutterfly-like inflated balloon of FIG. 3C. FIG. 3E shows a side view ofan elongated butterfly-like balloon with two ellipsoidal balloonchambers formed from a cylinder-like balloon. FIG. 3F shows across-section view of the elongated butterfly-like balloon of FIG. 3E.

FIGS. 4A-4C show device cross-sections during an exemplary method ofmanufacturing an inflatable balloon having two balloon chambers,according to many embodiments. FIG. 4A shows a cross-section of acylinder-like balloon disposed about a catheter shaft (shown in theinflated configuration). FIG. 4B shows the balloon after a first lengthof the inflatable balloon has been fixedly attached to the cathetershaft along a longitudinal axis of the catheter to form a firstlongitudinal bond extending thereon and generate a balloon having aheart-shaped cross-section about the catheter. FIG. 4C shows the balloonafter a second length of the inflatable balloon has been fixedlyattached to the catheter shaft along the longitudinal axis of thecatheter to form a second longitudinal bond extending thereon andgenerate a balloon having a butterfly-like or figure-eight shapedcross-section about the catheter.

FIGS. 5A-5D show perspective views of the inflatable balloon of FIGS. 4Aand 4C. FIG. 5A shows a perspective view of the balloon of FIG. 4A. FIG.5B shows a cross-section of the balloon of FIG. 5A. FIG. 5C shows aperspective view of the balloon of FIG. 4C. FIG. 5D shows across-section of the balloon of FIG. 5C.

FIGS. 6A-6D show different views of a balloon catheter device having twoellipsoidal balloon chambers, formed using the method described in FIGS.4A-4C, in the expanded configuration, according to many embodiments.FIG. 6A shows a top view of the device. FIGS. 6B and 6C show perspectiveviews of the device from different angles. FIG. 6D shows a bottom viewof the device.

FIGS. 7A-7C show a top views of another balloon catheter device,according to many embodiments. FIG. 7A shows a balloon catheter devicehaving two ellipsoidal balloon chambers, one balloon chamber foroccluding each of the left and right renal arteries, in a collapsedconfiguration. FIG. 7B shows the balloon catheter in an expandedconfiguration. FIG. 7C shows the balloon catheter in the expandedconfiguration inside a model abdominal aorta.

FIGS. 8A-8D show schematics position indication features suitable foruse with the balloon catheter devices disclosed herein to determine ifthe balloon catheter device has occluded the renal arteries, accordingto many embodiments. FIGS. 8A and 8B shows an axial view along theabdominal aorta depicting the relative positions of the left and rightballoon chambers in the initial position (FIG. 8A) and the “protective”or expanded position (FIG. 8B). FIGS. 8C and 8D show the positionindication feature in the initial position (FIG. 8C) and the “protected”or expanded position (FIG. 8D).

FIG. 9 shows an X-Ray image of the balloon catheter of FIGS. 7A-7Cinserted into a subject, with the balloon chambers in the “protective”position.

FIGS. 10A-10C show a balloon catheter having longitudinal positionindication features which can be used to determine the orientation ofthe balloon and if the balloon catheter occludes the renal arteries,according to many embodiments. FIG. 10A shows a perspective view of aballoon with a butterfly-like or figure-eight shaped cross-section aboutthe catheter and having a plurality of longitudinal position indicationfeatures extending thereon. FIG. 10B shows a cross-section perspectiveview of the balloon of FIG. 10A. FIG. 10C shows a side view of thedevice.

FIGS. 11A-11B show the deployment of the balloon catheter of FIGS.10A-10C, with the balloon chambers in the “protective” position insidethe aorta, according to many embodiments. FIG. 11A shows a cross-sectionview of the balloon catheter device of FIGS. 10A-10C deployed in anaorta, with the balloon chambers in the “protective” position. FIG. 11Bshows a lateral view of the balloon catheter device of FIGS. 10A-10Cdeployed in an aorta, with the balloon chambers in the “protective”position.

FIG. 12 shows an X-Ray image of the balloon catheter of FIG. 10Cinserted into a subject, with the balloon chambers in the “protective”position.

FIGS. 13A-13B show the deployment of the balloon catheter of FIGS.10A-10C, with the balloon chambers malpositioned inside the aorta,according to many embodiments. FIG. 13A shows a cross-section view ofthe balloon catheter device of FIGS. 10A-10C deployed in an aorta, withthe balloon chambers malpositioned. FIG. 13B shows a lateral view of theballoon catheter device of FIGS. 10A-10C deployed in an aorta, with theballoon chambers malpositioned.

FIG. 14 shows an exemplary time-delayed release mechanism suitable foruse with the balloon catheters disclosed herein, according to manyembodiments; the time-delayed release mechanism may be configured toautomatically collapse the inflatable balloon after a pre-determinedamount of time following deployment.

FIG. 15 shows a perspective view of a balloon catheter system, includingthe balloon catheter of FIGS. 7A-7C and the time-delayed releasemechanism of FIG. 14, according to many embodiments.

FIG. 16 shows a top view of another balloon catheter system, includingthe balloon catheter of FIGS. 10A-10C and the time-delayed releasemechanism of FIG. 14, according to many embodiments.

DETAILED DESCRIPTION

While various embodiments of the present disclosure have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions may occur to those skilled in theart without departing from the scope of the present disclosure. Itshould be understood that various alternatives to the embodiments of thepresent disclosure may be employed.

Provided herein are devices and systems that specifically focus onsolving one or both of the two main pathophysiological culprits ofCI-AKI—prolonged transit of contrast media inside the kidneys and renalouter medulla ischemia. In some embodiments, devices, systems, andmethods are provided for reducing contrast media concentrations oramounts entering the renal arteries to prevent AKI, for example, CI-AKI.Alternatively or in combination, some embodiments provide devices,systems, and methods for augmenting blood flow towards the renalarteries that feed the kidneys to treat or prevent renal ischemia.

In many embodiments, the device may comprise an occlusive element. Theocclusive element may comprise any of the balloons, membranes, orexpandable elements (e.g., mesh braid) described herein, inPCT/US2014/072302, and/or in PCT/US2017/031153. The occlusive elementmay, for example, be an inflatable balloon having at least two balloonchambers as described herein. The occlusive element may be disposed onor around a proximal portion of a catheter. The occlusive element may beadvanced into an abdominal aorta and positioned adjacent renal ostia ina collapsed configuration. The occlusive element may then be expanded(e.g., inflated) into an expanded configuration which is sized topartially or fully occlude or divert blood flow from the renal arteryostia while allowing blood flow over the catheter shaft. It will beunderstood by one of ordinary skill in the art that any of the occlusiveelements (e.g., balloons, membranes, braids, etc.) described herein orany of the features thereof may be combined as desired in order toarrive at a device for treating or preventing AKI. Any of the occlusiveelements, or any combination thereof, may be combined with any of theposition indication means or features, flow disturbing means orelements, flow pumps, sensors, flow augmentation means or elements,injection synchronizer, fluid balancer, time-delayed release mechanism,any other element described herein, in PCT/US2014/072302, and/or inPCT/US2017/031153, or any combination thereof, as desired by one ofordinary skill in the art, to arrive at a device for treating orpreventing AKI.

FIG. 1 shows a device for occluding vasculature of a subject, forexample, for treating or preventing AKI, for example, CI-AKI, comprisinga balloon catheter device. The device 100 may comprise a catheter 101and an inflatable balloon 102. The device 100 optionally may comprise aposition indication means, for example, a radio-opaque marker, on thetip of the catheter 101 or disposed on the inflatable balloon 102 asdescribed herein. The device 100 may be inserted into a blood vessel,for example, the abdominal aorta, of a patient and optionally positionedby monitoring the position of the radio-opaque marker for guidance. Thedevice 100 may be inserted into the abdominal aorta using either atrans-femoral arterial approach, a trans-brachial artery approach, or atrans-radial artery approach. The tip of the catheter 101, which may ormay not include a radio-opaque marker, may be situated so as to positionthe inflatable balloon 102 in the blood vessel, for example, thesupra-renal aorta, such that the inflatable balloon lies near theorifice(s) of the blood vessel, for example, the orifices of bilateralrenal arteries.

The position indication means may, for example, be a radio-opaquemarker, or other detectable marker, in order to improve visibility ofthe device during deployment, for example, with fluoroscopy orradiography.

The position indication means may, for example, be a radio-opaquemarker. One or more position indication means may be located on the tipof the catheter 101, on the inflatable balloon 102, or any combinationthereof. The position indication means may be used to monitor theposition of the device 100 upon insertion, during use, and/or duringremoval. The device 100 may be inserted into the abdominal aorta, forexample, by using either a trans-femoral arterial approach, atrans-brachial artery approach, or a trans-radial artery approach.

FIG. 2 shows the device 100 positioned in the supra-renal aorta near theorifices of the bilateral renal arteries. The inflatable balloon 102 maybe inflated such that the balloon 102 occludes the orifices of bothsides of the renal arteries. Occlusion of the renal arteries by thefirst balloon 102 may prevent a bolus influx of harmful agents, forexample, a contrast media, from flowing into the renal arteries from thesupra-renal aorta. Such occlusion may reduce the toxic effects of saidharmful agents by preventing delivery of the harmful agents to thekidney. The bolus of contrast media may be introduced using the samedevice 100 or a separate device that has been introduced either throughthe same or different path in the vasculature.

In some embodiments, the balloon may be fully inflated such that itsouter circumference contacts the aorta wall, heretofore defined as 100%inflation. In some embodiments, the balloon may be inflated to 90%, 80%,70%, 60%, 50%, 40%, or 30% of full inflation. The balloon mayalternatively or in combination be inflated within a range from about99.9% to about 10%, within a range from about 80% to about 20%, orwithin a range from about 70% to about 30%.

FIGS. 3A to 3D illustrate various embodiments of the inflatable balloon102. FIG. 3A shows an inflated balloon 102 positioned along andcirculating the catheter 101. FIG. 3B shows a cross-sectional view ofthe inflatable balloon 102 of FIG. 3A. The balloon may be positionedaround the catheter 101 such that a hollow area is formed between theinner edge of the balloon 102 and the catheter 101 to form a donut-likeballoon shape. By providing a hollow space inside of the balloon 102,blood may be allowed to flow along the catheter 101 when the balloon 102is inflated to occlude the orifices of both sides of the renal arteries.The balloon 102 may be inflated via at least one connection tube 304extending from the catheter 101 to the balloon 102. For example, theballoon may be inflated via four connection tubes 304 as shown in FIG.3B. FIG. 3C shows an alternative embodiment of the inflatable balloon102. The balloon 102 may be comprised of bilateral inflated balloonsections (also referred to herein as chambers) 303 a and 303 b to form abutterfly-like balloon shape. The sections 303 a and 303 b may beconnected to each side of catheter 101 via at least one connection tube304. Inflation of the balloon sections 303 a and 303 b may occlude theorifices of both sides of the renal arteries while also allowing bloodto flow along the catheter 101. FIG. 3D shows a cross-sectional view ofthe butterfly-like embodiment of the first balloon 102 depicted in FIG.3C. The balloon sections 303 a and 303 b may be connected to thecatheter 101 via one or more connection tube 304. For example, FIG. 3Ddepicts one connection tube per balloon section on each side of thecatheter 101. In some embodiments, the balloon may have one, two, three,four, five, or more connection tubes 304 to connect the first balloon102 to the catheter 101. The connection tube(s) may be used to provideinflation or deflation of the first balloon 102. FIGS. 3E-3F showanother embodiment of the inflatable balloon 102. FIG. 3E shows a sideview of an elongated butterfly-like balloon 102 with two ellipsoidalballoon chambers 303 a, 303 b formed from a cylinder-like balloon (asshown is FIGS. 4A-5D). The balloon 102 may be fixedly attached to thecatheter shaft 101 disposed coaxially therein so as to form at least twobilateral inflated balloon chambers 303 a and 303 b to form an axiallyelongated butterfly-like balloon shape. The chambers 303 a and 303 b maybe attached (e.g., bonded) to catheter 101 along at least one length ofthe inflatable balloon 102 along a longitudinal axis of the catheter101. Inflation of the balloon chambers 303 a and 303 b may occlude theorifices of both sides of the renal arteries while also allowing bloodto flow along the catheter 101. FIG. 3F shows a cross-section view ofthe elongated butterfly-like balloon of FIG. 3E. The balloon chambers303 a and 303 b may be coupled to the catheter 101 via one or morelongitudinal bonds as described herein. For example, FIG. 3F depicts twobonds to the catheter to form the two chambers 303 a, 303 b on each sideof the catheter 101.

In some embodiments, the inflatable balloon 102 may have a toroidal ordonut-like shape after inflation. In some embodiments, the inflatableballoon 102 may have a butterfly-like, figure-eight, or dumbbellcross-sectional shape about the catheter shaft 101 disposed thereinafter inflation.

In some embodiments, the catheter shaft may comprise a fluid outlet portdisposed within the balloon 102. The fluid outlet port may be in fluidcommunication with a source of inflation fluid (e.g., CO₂). The fluidoutlet port may be used to provide inflation or deflation of the firstballoon 102.

FIGS. 4A-4C show a method of manufacturing an inflatable balloon 102having two balloon chambers 303 a, 303 b. FIG. 4A shows a cross-sectionof a cylinder-like balloon (shown in the inflated configuration forclarity) disposed about a catheter shaft 101. In some embodiments, aninflatable balloon (e.g., an elongate tube or tunnel membrane) 102 maybe disposed about the catheter shaft 101 and bonded at its distal andproximal ends to the catheter shaft to form fluid tight seals andgenerate a cylinder-like balloon as shown in FIG. 4A. In someembodiments, the inflatable balloon 102 may be a standard cylindrical orbarrel balloon catheter. FIG. 4B shows the balloon 102 after a firstlength of the inflatable balloon 102 has been fixedly attached to thecatheter shaft 101 along a longitudinal axis of the catheter 101 to forma first longitudinal bond 505 a extending thereon and generate a balloonhaving a heart-shaped cross-section about the catheter with balloonchambers 303 a and 303 b. In some embodiments, the balloon 102 with theheart-shaped cross-section may, for example, be deployed in a bloodvessel as described herein. In some instances, one or more additionalbonds may be formed to generate balloon chambers as described herein.FIG. 4C shows the balloon 102 after a second length of the inflatableballoon has been fixedly attached to the catheter shaft 101 along thelongitudinal axis of the catheter 101 to form a second longitudinal bond505 b extending thereon, generating a balloon 102 having abutterfly-like or figure-eight shaped cross-section about the catheterwith balloon chambers 303 a and 303 b. Additional bonds may be formedusing the methods described herein as desired by one of ordinary skillin the art.

In some embodiments, the inflatable balloon 102 may comprise a firstballoon chamber 303 a and a second balloon chamber 303 b. The firstballoon chamber 303 a may be disposed on a first lateral side of theproximal portion of the catheter 101. The second balloon chamber 303 bmay be disposed on a second lateral side of the proximal portion of thecatheter 101.

In some embodiments, the first balloon chamber 303 a and second balloonchamber 303 b may each longitudinal cylindrical balloon chambers.

In some embodiments, the inflatable balloon 102 may comprise one balloonchamber. In some embodiments, the inflatable balloon 102 may comprise atleast two balloon chambers formed from a single balloon body as shown inFIG. 4C. The inflatable balloon 102 may comprise a plurality of balloonchambers, for example, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, or 20 chambers. It will be apparent to one of ordinary skillin the art that any number of chambers may be formed using the methodsdescribed herein as desired for a particular use or medical procedure.

In some embodiments, the one or more balloon chambers are formed byattaching the inflatable balloon to the catheter disposed coaxiallytherein along one or more lengths of the inflatable balloon along thelongitudinal axis of the catheter to form one or more longitudinal bondsextending thereon. The inflatable balloon 102 may, for example, beattached to the catheter with one longitudinal bond. The inflatableballoon 102 may, for example, be attached to the catheter with aplurality of longitudinal bonds, for example, 2, 3, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 longitudinal bonds.

In some embodiments, the one or more balloon chambers are formed byremovably attaching the inflatable balloon to the catheter disposedcoaxially therein.

In some embodiments, the one or more balloon chambers are formed byfixedly attaching the inflatable balloon to the catheter disposedcoaxially therein. In some embodiments, the one or more balloon chambersare formed by adhering the inflatable balloon to the catheter disposedcoaxially therein. In some embodiments, the one or more balloon chambersare formed by bonding the inflatable balloon to the catheter disposedcoaxially therein.

In some embodiments, the one or more balloon chambers are formed bybonding the inflatable balloon to the catheter disposed coaxiallytherein. The one or more balloon chambers may be formed by bonding theinflatable balloon to the catheter using one or more of the followingmethods: RF welding, adhesive bonding, thermal bonding, and the like.

FIGS. 5A-5D show perspective views of the inflatable balloon 102 ofFIGS. 4A and 4C. FIG. 5A shows a perspective view of the balloon 102 ofFIG. 4A. The inflatable balloon 102 may comprise a cylindrical balloondisposed coaxially about a catheter 101. FIG. 5B shows a cross-sectionof the balloon 102 of FIG. 5A. FIG. 5C shows a perspective view of theballoon 102 of FIG. 4C having first balloon chamber 303 a and secondballoon chamber 303 b. The first and second balloon chambers 303 a, 303b may be generated by forming first and second longitudinal bonds 505 a,505 b as described herein. FIG. 5D shows a cross-section of the balloonof FIG. 5C.

In some embodiments, the first balloon chamber 303 a and the secondballoon chamber 303 b may be in fluid communication with one another. Insome embodiments, the first balloon chamber 303 a and the second balloonchamber 303 b may be configured to inflate simultaneously.

In some embodiments, the first balloon chamber 303 a and the secondballoon chamber 303 b may be fluidly independent of one another.

In some embodiments, the first longitudinal bond 505 a may extend alength of the inflatable balloon 102 within a range of about 80% toabout 99% of the length of the inflatable balloon 102. The firstlongitudinal bond 505 a may, for example, extend 90% of the length ofthe inflatable balloon 102.

In some embodiments, the second longitudinal bond 505 b may extend alength of the inflatable balloon within a range of about 80% to about99% of the length of the inflatable balloon 102. The second longitudinalbond 505 a may, for example, extend 90% of the length of the inflatableballoon 102.

In some embodiments, one or more of the first and second longitudinalbonds 505 a, 505 b may extend less than the entire length of theinflatable balloon 102 (e.g., less than 100% of the length of theinflatable balloon) such that the first and second balloon chambers 303a, 303 b are in fluid communication with one another.

In some embodiments, the portion of the inflatable balloon 102 which isnot bonded to the catheter 101, for example, a portion of the inflatableballoon 102 near a proximal and/or distal end of the balloon 102, mayhave a cylindrical cross-section. In some instances, a fluid outlet portmay be disposed in the non-bonded section(s) in order to facilitatesimultaneous filling of the first and second balloon chambers 303 a, 303b.

In some embodiments, the distal and/or proximal end of the balloon 102may be bonded to the catheter 101 with a first longitudinal bond but nota second longitudinal bond. The portion of the inflatable balloon 102which is bonded to the catheter 101 only once may have a heart-shapedcross-section. In some instances, a fluid outlet port may be disposed inthe single-bonded section(s) in order to facilitate simultaneous fillingof the first and second balloon chambers 303 a, 303 b.

FIGS. 6A-6D show different views of a balloon catheter device 100 havingtwo ellipsoidal balloon chambers 303 a, 303 b, formed from aconventional barrel balloon catheter using the method described in FIGS.4A-4C, in the expanded configuration. FIG. 6A shows a top view of thedevice. FIGS. 6B and 6C show perspective views of the device 100 fromdifferent angles. FIG. 6D shows a bottom view of the device 100. Theballoon 102 may, for example, comprise a low durometer urethane bondedto the catheter 101 along about 60 mm of the about 70 mm body of theballoon.

FIGS. 7A-7C show a catheter device 2800 that may comprise a catheter 101with an inflatable balloon 102 disposed on a proximal portion thereof.The inflatable balloon 102 may comprise a first balloon chamber 303 adisposed on a first lateral side of the proximal portion of the catheter101. The inflatable balloon 102 may comprise a second balloon chamber303 b disposed on a second lateral side of the proximal portion of thecatheter 101, for example, opposite the first balloon chamber 303 a.

FIG. 7A shows a balloon catheter device 2800 having two ellipsoidalballoon chambers 303 a and 303 b of an expandable balloon 102 in acollapsed configuration. Device 2800 may be substantially similar todevice 100 described herein. FIG. 7B shows the device 2800 in anexpanded configuration. The first and second balloon chambers 303 a, 303b may, for example, be ellipsoidal as shown. The balloon chambers 303 a,303 b may form a dumb-bell or butterfly-like shape about the catheter101 in cross-section when expanded from the collapsed configuration(FIG. 7A) to the expanded configuration (FIG. 7B). The balloon chambers303 a, 303 b may be shaped so as to occlude the left and right renalarteries when expanded while allowing blood to flow between the balloonchambers 303 a, 303 b along the catheter shaft 101. As described herein,the balloon chambers 303 a, 303 b may be formed from a single balloondisposed about the catheter 101. As discussed further below, a positionindication feature 2900 may be disposed on the surfaces of the balloonchambers 303 a, 303 b to facilitate the determination of the positionand/or orientation of the balloon chambers 303 a, 303 b and/or whetherthe renal artery ostia are occluded as described herein. As shown inFIGS. 7A and 7B, the position indication feature 2900 may comprise aplurality of longitudinal radio-opaque markers and/or a radio-opaquemarker 2900 a disposed on the catheter 101 between the balloon chambers303 a, 303 b.

FIG. 7C shows the device 2800 in the expanded configuration inside amodel abdominal aorta 2850. The catheter balloon device 2800 is shownpositioned within a model abdominal aorta 2850. Generally, the one ormore balloon chambers 303 a, 303 b may be positioned adjacent theorifices of the right renal artery 210 and the left renal artery 211,for example, spanning between the supra-renal aorta 208 and theinfra-renal aorta 209, thereby controlling blood flow to any of theright renal artery 210, left renal artery 211, and/or infra-renal aorta209. While occluding the renal arteries 210, 211, the balloon chambers303 a, 303 b may not completely occlude the aorta 2850 and may allowblood flow through the gaps between the balloon chambers 303 a, 303 band the catheter 101. In cross-section, the expanded balloon chambers303 a, 303 b may assume a dumbbell or butterfly shape, for example, asdescribed herein. The inflatable balloon 102 may be deployed prior to orsimultaneously with injection of a contrast agent into the abdominalaorta 2850 of a patient so as to prevent the contrast agent fromentering the renal arteries 210, 211. After the bolus of contrast agenthas been introduced, the inflatable balloon 102 may be collapsed toallow blood flow to the renal arteries to resume.

Generally, the balloon chambers 303 a, 303 b may be of any size and/orshape. In particular the size and/or shape may be selected to controlthe amount of occlusion for each of the left and right arteries. Forexample, the renal arteries may be located at different distances downthe length of the aorta (e.g., viewing the aorta along the coronalplane, the left and right renal arteries may branch away from the aortaat different distances from the aortic arch). In such instances, it maybe beneficial to employ balloon chambers that are ellipsoidal (e.g.,greater in length along a longitudinal direction of the aorta than indiameter), thereby capable of occluding both the left and right renalartery upon being placed in the initial position. In some instances, therenal arteries may branch at different angles (as viewed along the axialplane) from the aorta between subjects or groups of subjects. In suchinstances, it may be beneficial to employ balloon chambers which arepositioned to match the branching architecture of the patient or groupof patients (e.g., balloon chambers which are positioned opposite oneanother on the catheter for patients with branching opposite one anotheror balloon chambers which are position less than 180° apart about thecatheter for patients with branching less than 180° apart). In someinstances, it may be beneficial to employ balloon chambers shaped todeform when contacting the aorta and “spread” along the wall in order toocclude a typical range of angles for a particular group of subjects. Insome instances it may be beneficial to employ balloon chambers sized orshaped to occlude a typical range of angles for a particular group ofsubjects. The typical range of angles may vary from subject group (e.g.,patient population) to subject group and the spread, angle, size, and/orshape of the balloon chambers may be configured to perform for aparticular subject group based on the typical range of branching angles.In some embodiments, the size and/or shape of the expandable balloon maybe specific for a particular group of subjects. For example, youngersubjects (e.g., under 15 years of age) may require balloon chambers thatare shorter in length and/or width (e.g., in an un-inflated state) ascompared to adults (e.g., 15 years of age and older). In anotherexample, balloon chambers of a particular size and/or shape may besuitable for subjects originating from a given geographical location orethnic background due to genetic and physiological variations betweensubjects or groups of subjects (e.g., Asians vs. Caucasians).Non-limiting examples of balloon length include about 1 millimeter (mm),about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm,about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm, about 13mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about 18 mm,about 19 mm, about 20 mm, about 21 mm, about 22 mm, about 23 mm, about24 mm, about 25 mm, about 26 mm, about 27 mm, about 28 mm, about 29 mm,about 30 mm, about 31 mm, about 32 mm, about 33 mm, about 34 mm, about35 mm, about 36 mm, about 37 mm, about 38 mm, about 39 mm, about 40 mm,41mm, about 42 mm, about 43 mm, about 44 mm, about 45 mm, about 46 mm,about 47 mm, about 48 mm, about 49 mm, about 50 mm, about 60 mm, about70 mm, about 80 mm, about 90 mm, about 100 mm, or greater than about 100mm. Non-limiting examples of balloon diameter include about 1 millimeter(mm), about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about7 mm, about 8 mm, about 9 mm, about 10 mm, about 11 mm, about 12 mm,about 13 mm, about 14 mm, about 15 mm, about 16 mm, about 17 mm, about18 mm, about 19 mm, about 20 mm, about 21 mm, about 22 mm, about 23 mm,about 24 mm, about 25 mm, about 26 mm, about 27 mm, about 28 mm, about29 mm, about 30 mm, about 31 mm, about 32 mm, about 33 mm, about 34 mm,about 35 mm, about 36 mm, about 37 mm, about 38 mm, about 39 mm, about40 mm, 41mm, about 42 mm, about 43 mm, about 44 mm, about 45 mm, about46 mm, about 47 mm, about 48 mm, about 49 mm, about 50 mm, about 60 mm,about 70 mm, about 80 mm, about 90 mm, about 100 mm, or greater thanabout 100 mm. In some embodiments, the diameter of the balloon (or oneor more balloon chambers) may change from a proximal end of the balloonto a distal end of the balloon. For example, the balloon (or one or moreballoon chambers) may be cigar-shaped, torpedo-shaped, orsubmarine-shaped. The balloon may be any shape suitable for occludingone or more arteries (e.g., renal arteries). Non-limiting examples ofballoon shapes include spherical, ellipsoidal, cylindrical, an n-sidedprism (pentagonal or hexagonal), where n is any number, conical, andpyramidal.

In some embodiments, one or more balloons or balloon chambers of thedevice may be inflatable. Inflation of the balloon may expand theballoon to occlude the artery. In some embodiments having two or moreballoon chambers, the balloon chambers may be fluidly-connected, and maybe inflated together. In other embodiments, the balloon chambers may notbe fluidly connected, and may be capable of independently inflating. Insome embodiments, the balloon chambers may be fluidly connected, whereina fluid connection may be opened or closed as needed, thereby allowinginflation of two or more balloon chambers together or inflation of eachballoon chamber separately. Any number of balloon chambers may be used.A device of the present disclosure may have a single balloon chamber. Adevice of the present disclosure may have two or more balloon chambers.Non-limiting examples of a multi-chambered balloon device include adevice comprising 2 balloon chambers, 3 balloon chambers, 4 balloonchambers, 5 balloon chambers, 6 balloon chambers, 7 balloon chambers, 8balloon chambers, 9 balloon chambers, 10 balloon chambers, and more than10 balloon chambers. In some embodiments, one or more balloon chambersof the device may be inflated, and the inflation of the balloonchamber(s) may be synchronized with an injection of a contrast dye(e.g., Urografin) into the subject. In some embodiments, the contrastdye injection may be performed prior to inflating the one or moreballoon chambers in the device. In some embodiments, the contrast dyeinjection may be performed simultaneously with the inflation of the oneor more balloon chambers in the device. In some embodiments, the one ormore balloon chambers in the device may be inflated prior to or afterinjection of the contrast dye into the subject.

FIGS. 8A-8D show a position indication feature 2900 which can be used todetermine if a balloon catheter device occludes the orifices of anartery such as the renal arteries. The renal arteries are not shown forsimplicity. FIGS. 8A-8B depict an axial view along the aorta 2850, forexample, an abdominal aorta, depicting the relative positions of thefirst 102 and second 103 catheter balloons in the initial position (FIG.8A) and the “protective” or inflated position (FIG. 8B). FIGS. 8C and 8Dshow the position indication feature 2900 in the initial position (FIG.8C) and the “protected” or expanded position (FIG. 8D). The positionindication feature 2900 may be used to help identify the position of thecatheter within the abdominal aorta 2850 and/or whether or not the renalarteries have been occluded upon expansion of the balloon chambers 303a, 303 b. The position indication feature 2900 may, for example,comprise one or more radio-opaque longitudinal markers as shown. Theradio-opaque longitudinal markers may be observed or monitored withinthe abdominal aorta during positioning of the occlusive element (e.g.,the inflatable balloon comprising first and second balloon chambers 303a, 303 b) within the abdominal aorta 2850 using x-ray imaging and usedto guide positioning of the occlusive element adjacent the renalarteries and/or confirm occlusion of the renal arteries. When unexpandedduring positioning (FIGS. 8A, 8C), the radio-opaque longitudinal markersmay appear straight within the abdominal aorta 2850. Expansion of theballoon chambers 303 a, 303 b and occlusion of the renal arteries mayconfirmed by the appearance of a bowed section, or “nipple”, in theradio-opaque longitudinal markers. FIG. 8D shows “nipples” 2901 and 2902which may be used as artery (e.g., renal artery) orifice locators. Such“nipples” 2901, 2902 may be formed when the balloon chambers 303 a, 303b are expanded and the flexible outer surface of the balloon chambers303 a, 303 b curve to partially enter and occlude the left and rightrenal artery ostia. In the initial, unexpanded configuration (FIGS. 8Aand 8C), the radio-opaque longitudinal markers 2900 are straight; and inthe protective, expanded position (FIGS. 8B and 8D), the outer mostradio-opaque longitudinal markers 2900 are curved outwardly at the renalarteria ostia.

Alternatively or in combination, at least a portion of the catheter 101,first balloon chamber 303 a, second balloon chamber 303 b, or anycombination thereof may comprise a radio-opaque material or radio-opaquemarker thereon as described herein. Alternatively or in combination, oneor more of the balloon chambers may have a radio-opaque material orradio-opaque marker coupled to (e.g., fixedly attached, painted on,etc.) the surface or interior of the one or more balloon chambers.Alternatively or in combination, one or more of the balloon chambers maybe inflated with a radio-opaque material as described herein. Similarbowing (e.g., “nipple” formation) may be observed with a balloon madeof, coupled to, or inflated with a radio-opaque material, for example.

FIG. 9 shows an X-Ray image of the device 2800 of FIGS. 7A-7C comprisinga first balloon chamber 303 a and a second balloon chamber 303 binserted into a subject, with the balloon chambers 303 a, 303 b expandedto be in the “protective” or occlusive position. Arrows identify“nipples” 2901 and 2902 which indicated that the expanded balloonchambers 303 a, 303 b have occluded the renal arteries as describedherein. For example, the balloon chambers 303 a, 303 b may be inflatedwith a radiopaque fluid such that the formation of the “nipples” 2901and 2902 are visible in X-Ray. In cases where the balloon chambers 303a, 303 b are expanded with a non-radiopaque fluid such as carbon dioxideor saline, the formation of the “nipples” 2901 and 2902 may be indicatedby observing the shape of radio-opaque longitudinal markers, such asthose described in FIGS. 8C-8D and FIGS. 10A-13B, on the surface of theballoon chambers 303 a, 303 b.

FIGS. 10A-10C show a balloon catheter device 1000 having longitudinalposition indication features 2900 which can be used to determine theorientation of the balloon and if the balloon catheter occludes therenal arteries. FIG. 10A shows a perspective view of a balloon 102having two balloon chambers 303 a, 303 b with a butterfly-like orfigure-eight shaped cross-section about the catheter 101 and having aplurality of longitudinal position indication features 2900 extendingthereon. FIG. 10B shows a cross-section perspective view of the balloonof FIG. 10A. FIG. 10C also shows the balloon of FIGS. 10A-10B. Theballoon 102 may, for example, comprise three longitudinal positionindication features 2900 painted on an external portion of each of theballoon chambers 303 a, 303 b. The longitudinal position indicationfeatures 2900 may, for example, comprise radio-opaque longitudinalmarkers as described herein. The balloon 102 may, for example, comprisea very low durometer urethane. The radio-opaque longitudinal markersmay, for example, comprise a radio-opaque ink which is painted orotherwise applied to the balloon 102. The radio-opaque ink may, forexample, comprise a silver-based radio-opaque material.

FIGS. 11A-11B show the deployment of the device 1000 of FIGS. 10A-10C,with the balloon chambers in the “protective” position inside the aorta2850. The device 1000 may be guided to a desired location within theabdominal aorta 2850 by monitoring a position indication means 2900, forexample, three radio-opaque longitudinal markers. FIG. 11A shows across-section view of the balloon catheter device of FIGS. 10A-10Cdeployed in an aorta, with the balloon chambers in the “protective”position with the balloon chambers 303 a, 303 b positioned to occludethe orifices of the renal arteries 210, 211. FIG. 11B shows a lateralview of the balloon catheter device of FIGS. 10A-10C deployed in anaorta, with the balloon chambers in the “protective” position. Theradio-opaque longitudinal markers 2900 may be used to help identify theposition of the catheter device 1000 within the abdominal aorta 2850and/or whether or not the renal arteries 210, 211 have been occludedupon expansion of the balloon chambers 303 a, 303 b. The radio-opaquelongitudinal markers 2900 may be observed or monitored within theabdominal aorta 2850 during positioning of the inflatable balloon 102comprising first and second balloon chambers 303 a, 303 b within theabdominal aorta 2850 using x-ray imaging and used to guide positioningof the inflatable balloon 102 adjacent the renal arteries 210, 211and/or confirm occlusion of the renal arteries 210, 211. When unexpandedduring positioning (FIGS. 10A-10C), the radio-opaque longitudinalmarkers may appear straight within the abdominal aorta 2850. Expansionof the balloon chambers 303 a, 303 b and occlusion of the renal arteries210, 211 may confirmed by the appearance of a bowed section, or“nipple”, in the radio-opaque longitudinal markers. FIG. 11B shows“nipples” 2901 and 2902 which may be used as artery (e.g., renal artery)orifice locators. Such “nipples” 2901, 2902 may be formed when theballoon chambers 303 a, 303 b are expanded and the flexible outersurface of the balloon chambers 303 a, 303 b curve to partially enterand occlude the left and right renal artery 210, 211 ostia. The“nipples” 2901, 2902 may form in part due to lower pressure in the renalarteries 210, 211 compared to the aorta 2850. In the initial, unexpandedconfiguration (FIGS. 10A-10C), the radio-opaque longitudinal markers2900 are straight; and in the protective, expanded position (FIGS.11A-11B), the radio-opaque longitudinal markers 2900 are curvedoutwardly at the renal arteria 210, 211 ostia.

FIG. 12 shows an X-Ray of the balloon catheter of FIG. 10C inserted intoa subject, with the balloon chambers in the “protective” position.Arrows identify “nipples” 2901 and 2902 in the radio-opaque longitudinalmarkers 2900 which indicated that the expanded balloon chambers 303 a,303 b have occluded the renal arteries as described herein. For example,the balloon chambers 303 a, 303 b may be inflated with a non-radiopaquefluid (e.g., carbon dioxide or saline) such that the formation of the“nipples” 2901 and 2902 by the radio-opaque longitudinal markers 2900 onthe surface of the balloon chambers 303 a, 303 b are visible in X-Ray.

FIGS. 13A-13B show the deployment of the embodiment of FIGS. 10A-10C,with the balloon chambers 303 a, 303 b malpositioned inside the aorta2850. FIG. 13A shows a cross-section view of the balloon catheter device1000 of FIGS. 10A-10C deployed in an aorta, with the balloon chambers303 a, 303 b malpositioned. FIG. 13B shows a lateral view of the ballooncatheter device 1000 deployed in an aorta 2850, with the balloonchambers 303 a, 303 b malpositioned such that the renal artery 210, 211ostia are not occluded upon inflation of the balloon 102. As describedherein, the radio-opaque longitudinal markers 2900 may be used to helpidentify the position of the catheter device 1000 within the abdominalaorta 2850 and/or whether or not the renal arteries 210, 211 have beenoccluded upon expansion of the balloon chambers 303 a, 303 b. Whenunexpanded during positioning (FIGS. 10A-10C), the radio-opaquelongitudinal markers may appear straight within the abdominal aorta 2850as described herein. Proper positioning of the balloon 102 in the aorta2850 may result in the appearance of “nipples” in the radio-opaquelongitudinal markers 2900 when expanded, as shown in FIGS. 11A-11B. Whenmalpositioned, as shown in FIGS. 13A-13B, the “nipples” may not bevisibly apparent. A lack of “nipples” in the radio-opaque longitudinalmarkers 2900 may indicate to the user (e.g., a physician) that theballoon 102 should be deflated and re-positioned with aorta 2850 beforefurther procedures are performed (such as contrast agent injection asdescribed herein).

The radio-opaque longitudinal markers 2900 may also be used to determinethe orientation of the device 1000 inside the abdominal aorta 2850 (orother blood vessel of interest to one of ordinary skill in the art). Theradio-opaque longitudinal markers 2900 may be configured to indicate theorientation of the inflatable balloon 102, in this example the first andsecond balloon chambers 303 a, 303 b, when positioned adjacent renalartery 210, 211 ostia of the subject. The orientation of the balloon 102(and balloon chambers 303 a, 303 b) may be important in the case wherethe balloon 102 is malpositioned between the renal arteries 210, 211ostia such that the ostia are not occluded as shown in FIGS. 13A-13B.The three radio-opaque longitudinal markers 2900 shown in FIGS. 11A-11Bmay be positioned on each of the balloon chambers 303 a, 303 b suchthat, when properly positioned in the “protective” position to occludethe ostia, the radio-opaqueness of each of the three markers 2900 issummed in the plane of the x-ray (taken along the lines 3000) shown inFIG. 11A, giving the appearance of very visible, dense line(s) underx-ray. When malpositioned as shown in FIG. 13A, the lines may not besummed and may therefore be less visible in the x-ray. Therefore, thedensity (e.g., visibility) of the lines under x-ray may inform the useras to the orientation of the balloon 102 (and balloon chambers 303 a,303 b).

Any of the devices described herein may further comprise a time-delayedrelease mechanism configured to automatically collapse the inflatableballoon after a pre-determined amount of time following deployment(i.e., inflation). The time-delayed release mechanism may be provided ona handle or controller of the device.

For example, the catheter shaft device 100, 1000, or 2800 may furthercomprise a time-delayed release mechanism configured to automaticallycollapse the expandable mesh braid after a pre-determined amount of timefollowing deployment. The time-delayed release mechanism may, forexample, comprise an energy accumulation and storage component and atime-delay component. For example, the time-delayed release mechanismmay comprise a spring with a frictional damper, an example of which isdescribed in FIG. 14. The energy accumulation and storage component may,for example, be a spring or spring-coil or the like. The time-delayedrelease mechanism may, for example, be adjustable by one or more of theuser, the manufacturer, or both. The time-delayed release mechanism mayfurther comprise a synchronization component to synchronize theinjection of a contrast media or other harmful agent with the opening orclosing of the catheter shaft device. For example, injection may besynchronized with occlusion of the renal arteries by the expandable meshbraid such that a contrast media may be prevented from entering therenal arteries.

FIG. 14 shows an embodiment of a time-delayed release mechanism 3100configured to automatically collapse the inflatable balloon after apre-determined amount of time following deployment. Any of the devicesdescribed herein may further comprise a time-delayed release mechanism3100. The time-delayed release mechanism 3100 may be configured tofacilitate expansion and subsequent collapse any of the expandableocclusive elements described herein after a pre-determined amount oftime following deployment or expansion of the occlusive element (e.g.,inflatable balloon). For example, the time-delayed release mechanism3100 may be used to automatically deflate an inflatable balloon after apre-determined amount of time. The time-delayed release mechanism may,for example, comprise an energy accumulation and storage component and atime-delay component. For example, the time-delayed release mechanismmay comprise a spring with a frictional damper. The energy accumulationand storage component may, for example, be a spring or spring-coil orthe like. The time-delayed release mechanism 3100 may, for example,comprise a syringe 3110 and a spring 3120 disposed around a syringe pump3130. The tip 3150 of the syringe 3110 may be configured to attach tothe distal end of the catheter device (not shown), for example, via apress-fit, screw-fit, or luer-lock connector. The release mechanism 3100may further comprise a handle 3140 which the user may grip whiledepressing the syringe pump 3130 and attached spring 3120 into thesyringe 3110 to expand the inflatable balloon (not shown). Actuation ofthe syringe pump 3130 may, in the case of a balloon catheter, forexample, force a fluid (e.g., liquid or gas) into the balloon(s) via thetip connection 3150 to the catheter device in order to inflate andexpand the balloon (e.g., expand one or more of the balloon chambers) toan expanded configuration. Removal of the pressure applied to thesyringe pump 3130 may cause the spring 3120 to release the energy itaccumulated by being depressed and quickly retract the syringe pump 3130from its depressed position within the syringe 3110 to deflate andcollapse the balloon after a pre-determined amount of time. Thetime-delayed release mechanism 3120 may further comprise a frictionaldamper configured to introduce the pre-determined amount of time betweenthe inflation of the balloon, release of the syringe pump 3130, and therelease of energy by the spring 3120. It will be understood by one ofordinary skill in the art that the amount of friction applied by thedamper to the syringe pump 3130 and/or spring 3120 may be calibrated togenerate any pre-determined time-delay desired such as by providing thespring 3120 with various spring constants depending on the time-delaydesired.

The time-delayed release mechanism 3100 may, for example, be adjustableby one or more of the user, the manufacturer, or both. The time-delayedrelease mechanism 3100 may further comprise a synchronization componentto synchronize the injection of a contrast media or other harmful agentwith the opening or closing of the balloon catheter shaft device asdescribed herein. For example, injection may be synchronized withocclusion of the renal arteries by the first and second balloon chamberssuch that a contrast media may be prevented from entering the renalarteries.

FIG. 15 shows a further embodiment of the present disclosure includingthe catheter device 2800 of FIGS. 7A-7C and the time-delayed releasemechanism 3100 of FIG. 14. The catheter device 2800 may comprise acatheter 101 with a first balloon chamber 303 a and a second balloonchamber 303 b on a proximal portion thereof as described herein. Adistal portion 3200 of the catheter 101 may comprise a connectionelement 3210 configured to connect to the tip 3150 of the time-delayedrelease mechanism 3100. The distal portion 3200 of the catheter 101 maybe configured to remain external to the subject when the first andsecond balloon chambers 303 a, 303 b are positioned adjacent the renalarteries of the subject. The catheter 101 and the syringe 3110 may befluidly connected, for example, to allow a fluid to pass from thesyringe 3110 to the catheter 101 and into the balloon chambers 303 a,303 b via the catheter 101. Actuation of the time-delayed releasemechanism 3100 may expand the balloon chambers 303 a, 303 b with thefluid as described herein. The distal portion 3200 of the catheter 101may comprise one or more infusion port 3220 as described herein. Theinfusion port 3220 may, for example, be configured to infuse amedication or other fluid (e.g., normal saline) into the aorta, forexample via a side aperture in the catheter 101 (not shown). The distalportion 3200 of the catheter 101 may further comprise one or moreorientation indication feature 3230. The orientation indication feature3230 may be configured to indicate the orientation of the occlusiveelement, in this example the first and second balloon chambers 303 a,303 b, when positioned adjacent renal artery ostia of the subject. Theorientation indication feature 3230 may, for example, comprise one ormore of a visible marking, a protrusion, a wing, a flag, or the like.The orientation indication feature 3230 may be aligned with the firstand second balloon chambers 303 a, 303 b in a particular manner suchthat the orientation of the orientation indication feature 3230 outsideof the subject may be indicative of the orientation of the first andsecond balloons 102, 103 inside the subject. For example, theorientation indication feature 3230 may comprise a pair of wings asshown which include a first wing aligned (i.e., facing the same radiallyoutward direction as) with the first balloon chamber 303 a and a secondwing aligned with (i.e., facing the same radially outward direction as)the second balloon chamber 303 b. The catheter 101 may be sufficientlystiff such the orientation indication feature 3230 maintains alignmentwith the balloon chambers 303 a, 303 b as the catheter 101 is torqued orrotated. For example, the orientation indication feature 3230 may beconfigured to lie approximately parallel to (or alternatively faceperpendicularly away from or towards, or be otherwise oriented inrelation to) the ground when the first and second balloon chambers 303a, 303 b are properly positioned within the abdominal aorta adjacent therenal arteries of the subject. Alternatively or in combination, the oneor more position indication features may be used to determine theorientation of the balloon chambers 303 a, 303 b within the abdominalaorta as described herein. It will be understood by one of ordinaryskill in the art that any of the catheter devices described herein maybe attached to a time-delayed release mechanism 3100, comprise one ormore infusion port 3220, and/or comprise one or more orientationindication feature 3230 in a similar manner as described herein.

FIG. 16 shows another embodiment of the present disclosure including theballoon catheter device 1000 of FIGS. 10A-10C and the time-delayedrelease mechanism 3100 of FIG. 14. The catheter device 1000 may comprisea catheter 101 with a first balloon chamber 303 a and a second balloonchamber 303 b on a proximal portion thereof as described herein. Adistal portion 3200 of the catheter 101 may comprise a connectionelement 3210 configured to connect to the tip 3150 of the time-delayedrelease mechanism 3100. The distal portion 3200 of the catheter 101 maybe configured to remain external to the subject when the first andsecond balloon chambers 303 a, 303 b are positioned to occlude the renalarteries of the subject. The balloon 102 may comprise longitudinalposition indication features, or radio-opaque longitudinal markers 2900painted on an external portion of each of the balloon chambers 303 a and303 b. The radio-opaque longitudinal markers 2900 may be used to helpidentify the position of the catheter device 1000 within the abdominalaorta and/or whether or not the renal arteries have been occluded uponexpansion of the balloon chambers 303 a, 303 b. The catheter 101 and thesyringe 3110 may be fluidly connected, for example, to allow a fluid topass from the syringe 3110 to the catheter 101 and into the balloonchambers 303 a, 303 b via the catheter 101. Actuation of thetime-delayed release mechanism 3100 may expand the balloon chambers 303a, 303 b with the fluid as described herein. The distal portion 3200 ofthe catheter 101 may comprise one or more infusion port 3220 asdescribed herein. The infusion port 3220 may, for example, be configuredto infuse a medication or other fluid (e.g., normal saline) into theaorta, for example via a side aperture in the catheter 101 (not shown).The distal portion 3200 of the catheter 101 may further comprise one ormore orientation indication feature 3230. The orientation indicationfeature 3230 may be configured to indicate the orientation of theocclusive element, in this example the first and second balloon chambers303 a, 303 b, when positioned to occlude the orifices of the renalarteries of the subject. The orientation indication feature 3230 may,for example, comprise one or more of a visible marking, a protrusion, awing, a flag, or the like. The orientation indication feature 3230 maybe aligned with the first and second balloon chambers 303 a, 303 b in aparticular manner such that the orientation of the orientationindication feature 3230 outside of the subject may be indicative of theorientation of the balloon 102 inside the subject. For example, theorientation indication feature 3230 may comprise a pair of wings asshown which include a first wing aligned (i.e., facing the same radiallyoutward direction as) with the first balloon chamber 303 a and a secondwing aligned with (i.e., facing the same radially outward direction as)the second balloon chamber 303 b. The catheter 101 may be sufficientlystiff such the orientation indication feature 3230 maintains alignmentwith the balloon chambers 303 a, 303 b as the catheter 101 is torqued orrotated. For example, the orientation indication feature 3230 may beconfigured to lie approximately parallel to (or alternatively faceperpendicularly away from or towards, or be otherwise oriented inrelation to) the ground when the first and second balloon chambers 303a, 303 b are properly positioned to occlude the orifices of the renalarteries of the subject. Alternatively or in combination, the one ormore position indication features may be used to determine theorientation of the balloon chambers 303 a, 303 b within the abdominalaorta as described herein. It will be understood by one of ordinaryskill in the art that any of the catheter devices described herein maybe attached to a time-delayed release mechanism 3100, comprise one ormore infusion port 3220, and/or comprise one or more orientationindication feature 3230 in a similar manner as described herein.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the scope of the present disclosure.It should be understood that various alternatives to the embodimentsdescribed herein may be employed in practicing the inventions of thepresent disclosure. It is intended that the following claims define thescope of the invention and that methods and structures within the scopeof these claims and their equivalents be covered thereby.

What is claimed is:
 1. A device for occluding vasculature of a subject,the device comprising: a catheter shaft comprising a proximal portionand a distal portion; and an inflatable balloon disposed on the proximalportion of the catheter shaft, wherein the inflatable balloon comprisesa first balloon chamber and a second balloon chamber, the first andsecond balloon chambers being formed by one or more of (i) fixedlyattaching a first length of the inflatable balloon to the catheter shaftalong a longitudinal axis of the catheter to form a first longitudinalbond extending thereon or (ii) fixedly attaching a second length of theinflatable balloon to the catheter shaft along the longitudinal axis ofthe catheter to form a second longitudinal bond extending thereon,wherein the inflatable balloon has an expanded configuration which, whenadvanced into a blood vessel and positioned adjacent blood vessel ostiaof the subject, is sized to occlude the blood vessel ostia whileallowing blood flow over the catheter shaft, and wherein the distalportion is configured to remain outside a body of the subject when theproximal portion is positioned adjacent blood vessel ostia of thesubject.
 2. The device of claim 1, wherein the first balloon chamber isdisposed on a first lateral side of the proximal portion and the secondballoon chamber is disposed on a second lateral side of the proximalportion.
 3. The device of claim 1, wherein the first balloon chamber andsecond balloon chamber are each longitudinal cylindrical balloonchambers.
 4. The device of claim 1, wherein the first balloon chamberand the second balloon chamber are in fluid communication with oneanother.
 5. The device of claim 1, wherein the first balloon chamber andthe second balloon chamber are configured to inflate simultaneously. 6.The device of claim 1, wherein the first longitudinal bond extends 80%of the length of the inflatable balloon.
 7. The device of claim 1,wherein the second longitudinal bond extends 90% of the length of theinflatable balloon.
 8. The device of claim 1, wherein the inflatableballoon comprises a figure-eight, dumbbell, or butterfly-like crosssection about the catheter shaft disposed therein.
 9. The device ofclaim 1, further comprising one or more position indication featuresdisposed on the expandable balloon.
 10. The device of claim 9, whereinthe one or more position indication feature comprises one or moreradio-opaque markers.
 11. The device of claim 9, wherein the one or moreradio-opaque marker comprises one or more radio-opaque longitudinalmarkers.
 12. The device of claim 11, wherein the one or moreradio-opaque longitudinal markers comprises a plurality of radio-opaquelongitudinal markers disposed on the expandable balloon along alongitudinal axis of the expandable balloon.
 13. The device of claim 11,wherein the one or more radio-opaque longitudinal markers are configuredto indicate the orientation of the expandable balloon when positionedadjacent renal artery ostia of the subject.
 14. The device of claim 11,wherein the one or more radio-opaque longitudinal markers are configuredto change from a straight configuration to a bowed configuration whenexpanded adjacent blood vessel ostia of the subject.
 15. The device ofclaim 1, wherein fixedly attaching comprises adhering.